HbA1c and hypoglycaemia in intensively treated type 2 diabetes: a retrospective cohort study in primary care.

Objective: To establish whether low HbA1c is associated with clinical hypoglycaemia among people with type 2 diabetes prescribed insulins or sulphonylureas. Design: Retrospective cohort study using routine electronic GP health records collected between January 2013 and December 2015. Setting: Three east London Clinical Commissioning Groups. Participants: Two cohorts of adults with type 2 diabetes prescribed either (i) insulins with or without other oral antidiabetic medication (n = 6788, 36.4%) or (ii) sulphonylureas with or without other oral antidiabetic medications excluding insulins (n = 11,840, 63.6%). Main outcome measures: First clinically recorded hypoglycaemia and all-cause mortality. Hazard ratios (HR) adjusting for age, ethnicity, renal function and comorbidities were calculated using Cox regression models. Results: Compared with an HbA1c of 53-63 mmol/mol, the adjusted HR of hypoglycaemia in those with a low HbA1c, below 53 mmol/mol, in the insulin and sulphonylurea cohorts were 1.26 (95% CI, 0.97 to 1.62) and 1.54 (95% CI, 1.27 to 1.87), respectively. Adjusted HRs of all-cause mortality from low HbA1c in the insulin and sulphonylurea cohorts were 1.54 (95% CI, 1.15 to 2.07) and 1.42 (95% CI, 1.11 to 1.81), respectively. Increasing age and renal impairment were also associated with increased hypoglycaemic risk in both cohorts. Conclusions: HbA1c below 53 mmol/mol was associated with episodes of clinical hypoglycaemia among people with type 2 diabetes prescribed sulphonylureas, and all-cause mortality in those prescribed insulins and sulphonylureas. These findings support the need for reviewing glycaemic targets and the intensities of treatment in those with low HbA1c prescribed insulins or sulphonylureas to reduce the risk of hypoglycaemia